Characterization of Sexual Dimorphism in the Brain

大脑性别二态性的表征

• 批准号: 10166218
• 负责人: Nirao Mahesh Shah
• 金额: $ 9.01万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166218
• 关键词: Androgens; Animals; Aromatase; Brain; Brain region; Cells; Diagnostic; Disease; Enzymes; Estrogens; Female; Fiber; Functional disorder; Future; Goals; Health; Heart; Hypothalamic structure; Label; Light; Link; Medial; Mental disorders; Microscopic; Molecular; Nerve Degeneration; Neurologic; Neuronal Dysfunction; Neurons; Partner in relationship; Pathway interactions; Photometry; Physiological; Physiology; Regulation; Reproductive Behavior; Research; Rewards; Rodent; Social Interaction; Stress; Structure of terminal stria nuclei of preoptic region; Testing; Testosterone; Therapeutic; Work; brain behavior; insight; mature animal; neural circuit; parent project; response; sex; sexual dimorphism; stressor

Project Summary Social interactions are powerfully modulated by internal physiological state and future goals. The goal of our project is a functional and molecular characterization of the mammalian bed nucleus of the stria terminalis (BNST), with a focus on its medial division posteromedial compartment (BNSTmpm). The BNSTmpm is sexually dimorphic across many mammalian species, and it has been implicated in a diversity of social interactions in both sexes and physiological responses. Consistent with these observations, BNSTmpm neurons express the enzyme aromatase that converts testosterone or related androgens into estrogens; aromatase activity is essential for wildtype sexual differentiation of the brain and behavior in both sexes in rodents and many other animals. However, the function of aromatase in different brain regions in adult animals remains poorly characterized. The research goals of the diversity supplement fit within the goals of the parent project, and in particular they are focused on a subset of the specific aims. We have identified a small subset of BNSTmpm neurons that are activated upon mating in females. In aim 1 of the supplement, we will use FosTrap to label these neurons and use fiber photometry to understand the specific components of mating that activate these cells. We will next use chemogenetic actuators to test if these mating-activated BNSTmpm neurons are necessary or sufficient for female reproductive behaviors. In aim 2 of the supplement, we will specifically delete aromatase in BNSTmpm neurons to test its functional contribution to sexually dimorphic social interactions and physiology in both sexes. In summary, the studies proposed for the diversity supplement fit within the overarching goals of the parent project. Health Relatedness: Neurodegenerative and psychiatric conditions often reflect dysfunction of neural circuitry at a gross or microscopic level, and these remain poorly understood and therapeutically intractable. The BNST is a critical node linking amygdalar, hypothalamic, and cortical networks in the regulation of social interactions, response to various stressors, and reward pathways. Our proposed studies will shed light on the connectivity and functions of a subset of BNST neurons in the two sexes, thereby leading to an advance in basic scientific understanding of this region and the neural circuits within which it functions in health, and it may ultimately provide insights into future therapeutic or diagnostic applications for mental illness and common neurodegenerative conditions.

项目摘要 社会互动受到内部生理状态和未来目标的有力调节。我们的目标 项目是哺乳动物终纹床核的功能和分子特征 （BNST），重点是其内侧部后内侧室（BNSTmpm）。BNSTmpm在性方面 它在许多哺乳动物物种中具有二态性，并且与多种社会互动有关， 性别和生理反应。与这些观察结果相一致，BNSTmpm神经元表达 将睾酮或相关雄激素转化为雌激素的芳香酶;芳香酶活性是 在啮齿类动物和许多其他动物中，对大脑的野生型性分化和两性行为至关重要 动物然而，芳香化酶在成年动物不同脑区的功能仍然很差 表征了多样性补充的研究目标符合母项目的目标， 特别是，它们侧重于具体目标的一个子集。我们已经确定了BNSTmpm的一个小子集 雌性交配时激活的神经元。在补充的目标1中，我们将使用FosTrap标记 并使用纤维光度学来了解激活这些神经元的交配的特定成分。 细胞接下来，我们将使用化学致动器来测试这些交配激活的BNSTmpm神经元是否 是女性生殖行为所必需的或足够的。在补充文件的目的2中，我们会特别删除 芳香化酶的BNSTmpm神经元，以测试其功能的贡献，性二态社会互动， 两性的生理学。总之，为多样性补充提出的研究适合于 父项目的总体目标。 健康相关性：神经退行性疾病和精神疾病通常反映神经回路功能障碍 在宏观或微观水平上，这些仍然知之甚少，治疗上难以解决。在BNST 是连接杏仁核、下丘脑和皮质网络调节社会互动的关键节点， 对各种压力的反应和奖励途径。我们提出的研究将阐明 和功能的一个子集的BNST神经元在两种性别，从而导致了一个进步的基础科学 了解这个区域和它在健康中发挥作用的神经回路，它最终可能 为未来的精神疾病治疗或诊断应用提供见解， 神经退行性疾病